Analysis of Immunological and Clinical Response to Vaccination Against Sars-COV-2 in Patients with Chronic Myeloid Leukemia

ZURDO Castronuño, Alejandro

Oral and Poster Abstracts
632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster I

Research, Fundamental Science, Biological therapies, Clinical Research, CML, Chronic Myeloid Malignancies, Diseases, real-world evidence, Therapies, immunology, Myeloid Malignancies, Biological Processes, Vaccines

Alejandro ZURDO Castronuño¹^*, Miriam Solera Sainero²^*, Magdalena Corona³^*, Monserrat Torres⁴^*, Guiomar Casado-Fernandez⁴^*, Fernando Ramos-García⁵^*, Javier Garcia-Pérez⁴^*, María Aranzazú Murciano-Antón⁶^*, María Jesús Blanchard, MD⁷^*, Juan Marquet Palomanes, MD⁸^*, Fernando Martin Moro, MD⁷^*, Mayte Pérez-Olmeida⁹^*, Javier López Jiménez, MD, PhD⁷^*, Maria Teresa Coiras⁴^*, Sara Rodriguez-Mora⁴^* and Valentín Garcia-Gutiérrez, MD, PhD⁷

¹Hematology and Hemotherapy service, HOSPITAL UNIVERSITARIO RAMÓN Y CAJAL, MADRID, AL, Spain
²Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain., MADRID, Spain
³HOSPITAL UNIVERSITARIO RAMÓN Y CAJAL, Madrid, Spain
⁴Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain
⁵Instituto De Salud Carlos III, Majadahonda, ESP
⁶Family Medicine, Centro de Salud Doctor Pedro Laín Entralgo, Alcorcón, Spain
⁷Hematology Service, Hospital Universitario Ramón y Cajal, Madrid, Spain
⁸Hematology Service, Hospital Universitario Ramón y Cajal, Madrid, 28012, Spain
⁹Serology Laboratory, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain

Background: Patients with oncohematological malignancies have been excluded from the clinical trials in which the vaccines against COVID-19 were approved. Although there are some studies that have evaluated the immunologic and clinical response to SARS-CoV-2 in patients with different oncohematologic diseases, the response developed by patients with Chronic Myeloid Leukemia (CML) has been little explored.

Objective: To evaluate the immune and clinical response to vaccination against SARS-CoV-2 in patients with CML.

Materials and methods: We prospectively studied the humoral and cellular immune response to SARS-CoV-2 before and 1 month after receiving two doses of a COVID-19 mRNA vaccine in CML patients (n=29) compared to healthy donors (n=24). Among the CML patients, 5/29 (17%) had not received active treatment with tyrosine kinase inhibitors in the previous 12 months. Direct cellular cytotoxicity (DCC) studies of peripheral blood cells (PBMCs) against pseudotyped SARS-CoV-2 infec- ted Vero E6 cells were performed by measuring Caspase-3 activation and cytotoxic populations were phenotyped by flow cytometry. Antibody-dependent cell-mediated cytotoxicity (ADCC) analysis was performed using Raji cells as the target of PBMCs and quantifying apoptosis induction by measuring the levels of Annexin V.

Results: 1) CML patients presented an early humoral response against COVID-19 similar to healthy donors, with a 5-fold increase over baseline values (p<0.0001). 2) No differences in neutralizing antibody titers against SARS-CoV-2 were observed between CML patients and healthy donors. 3) CCDA studies showed similar responses between CML patients and healthy donors, with no increase in this response after 1 month receiving two doses of the vaccine (Figure 1A). 4) CCD studies showed higher baseline activity in PBMCs from CML patients, probably due to immunomodulatory treatment or the disease itself, although the results did not reach statistic significance (Figure 1B), these results being maintained independently of the populations studied (CD8; NK (CD3-CD56+); CD3+CD8±TCRgd+). 5) No significant differences were observed between the response developed by patients with CML on active treatment compared to those in the treatment-free phase. 6) A total of 10 breakthrough infections were observed in vaccinated patients, all of which were mild.

1707 Analysis of Immunological and Clinical Response to Vaccination Against Sars-COV-2 in Patients with Chronic Myeloid Leukemia